Bromine → 2-Amino-5-methyl-4,5,6-trihydrobenzothiazol-7-one

HRID 595084Notes

Reaction equation

HRID 595084 reaction equation
[CH3:1][CH:2]1[CH2:7][C:6](=[O:8])[CH2:5][C:4](=O)[CH2:3]1.CC([O-])=O.[Na+].BrBr.[NH2:17][C:18]([NH2:20])=[S:19]>CC(O)=O>[NH2:20][C:18]1[S:19][C:5]2[C:6](=[O:8])[CH2:7][CH:2]([CH3:1])[CH2:3][C:4]=2[N:17]=1

Participants

6

Reactant 4

HCID 24408BromineHCID 4580955-Methylcyclohexane-1,3-dioneHCID 517045Sodium AcetateHCID 2723790Thiourea

Product 1

HCID 27565102-Amino-5-methyl-4,5,6-trihydrobenzothiazol-7-oneYield 86.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

5-Methyl-cyclohexane-1,3-dione (70.0 g, 0.555 mol) and NaOAc (68.3 g, 0.832 mol) are suspended in AcOH (700 mL) and Br2 (88.7 g, 0.555 mol) is added drop-wise while maintaining the reaction temperature between 15 and 20° C. After complete addition, the reaction is stirred at RT overnight. Thiourea (42.2 g, 0.555 mol) is added in portions and the reaction mixture is heated to 100° C. for 1 h. After cooling to RT, the AcOH is removed in vacuo. The resulting crude product is diluted with water (1 L), adjusted to pH=7 with NaHCO3 solution (3 M) and the resulting mixture is extracted with EtOAc (3×1 L). The organic phase is washed with brine and dried over anhydrous Na2SO4. The solvent is evaporated in vacuo and the residue is recrystallized from hexane to give 2-amino-5-methyl-5,6-dihydro-4H-benzothiazol-7-one (87.2 g, 86% yield).

Workup

  1. temperaturewhile maintaining the reaction temperature between 15 and 20° C
  2. additionAfter complete addition
  3. temperaturethe reaction mixture is heated to 100° C. for 1 h
  4. temperatureAfter cooling to RT
  5. customthe AcOH is removed in vacuo
  6. additionThe resulting crude product is diluted with water (1 L)
  7. extractionthe resulting mixture is extracted with EtOAc (3×1 L)
  8. washThe organic phase is washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. customThe solvent is evaporated in vacuo
  11. customthe residue is recrystallized from hexane

Sources & evidence

ORD record
ord-4256d8ac48eb4ff2aeeb0c519e5d7866
Source dataset
uspto-grants-2016_01
Patent number
US09243000B2

Reaction notes

Loading…